# US 10,500,526 B1 · Method and device for high-throughput solution exchange for cell and particle suspensions

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- Number: US 10,500,526 B1
- Document ID: US10500526B1
- Status: Granted
- Kind: B1
- Application number: 16/263,232
- Filed: 2019-01-31
- Granted: 2019-12-10
- Earliest claimed: 2010-11-18
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Dino Di Carlo; Daniel R. Gossett; Henry T. K. Tse
- Web page: https://patentgrep.com/patent/US10500526B1

## CPC

- B01D 12/00: Displacing liquid, e.g. from wet solids or from dispersions of liquids or from solids in liquids, by means of another liquid
- B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules}
- B01L 3/502776: {specially adapted for focusing or laminating flows}
- B01L 3/502746: {characterised by the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves}
- B01L 2200/0652: Sorting or classification of particles or molecules
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2400/0487: fluid pressure, pneumatics
- B01L 2400/084: Passive control of flow resistance
- G01N 15/149: specially adapted for sorting particles, e.g. by their size or optical properties
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A method of exchanging fluids with suspended particles includes providing a microfluidic device with a first inlet channel operatively coupled to a source of particles and a second inlet channel operatively coupled to an exchange fluid. A transfer channel is connected at a proximal end to the first inlet channel and the second inlet channel. First and second outlet channels are connected to a distal end of the transfer channel. The source of particles is flowed at a first flow rate into the first inlet channel while the exchange fluid is flowed at a second flow rate into the second inlet channel wherein the ratio of the second flow rate to the first flow rate is at least 1.5. Particles are collected in one of the first and second outlet channels while fluid substantially free of particles is collected in the other of the first and second outlet channels.

## Claims

### Claim 1

A method of transferring particles across fluid streamlines comprising:
providing a microfluidic device comprising a first inlet channel operatively coupled to a source of fluid containing particles suspended therein, a second inlet channel operatively coupled to a source of exchange fluid, a transfer channel having a proximal end and a distal end, the proximal end of the transfer channel connected to the first inlet channel and the second inlet channel, and a plurality of outlet channels connected to the distal end of the transfer channel;
flowing the fluid containing particles suspended therein at a first flow rate into the first inlet channel;
flowing the exchange fluid at a second flow rate into the second inlet channel, wherein a co-flow state of the fluid containing the particles suspended therein and the exchange fluid is maintained along substantially all of the transfer channel, wherein at least some of the particles of the fluid containing the particles suspended therein migrate in response to inertial lift forces toward an equilibrium position (Xeq) located in the exchange fluid; and
collecting the migrated particles into a first outlet channel of the plurality of outlet channels.

### Claim 2 (depends on 1)

The method of claim 1, further comprising collecting fluid substantially free of the migrated particles in another of the plurality of outlet channels.

### Claim 3 (depends on 1)

The method of claim 1, wherein the particles comprise cells.

### Claim 4 (depends on 1)

The method of claim 1, wherein the particles comprise white blood cells (WBCs).

### Claim 5 (depends on 1)

The method of claim 1, wherein the fluid containing particles comprises blood.

### Claim 6 (depends on 1)

The method of claim 1, wherein the first inlet channel comprises a focusing region comprising a plurality of curves.

### Claim 7 (depends on 1)

The method of claim 1, wherein a Particle Reynolds number for the migrated particles in the transfer channel is between about 0.25 and 1.87.

### Claim 8 (depends on 2)

The method of claim 2, wherein the plurality of outlet channels have different dimensions to provide differing fluidic resistances for the plurality of outlet channels.

### Claim 9 (depends on 8)

The method of claim 8, wherein the different dimensions comprise a width dimension that is varied in the plurality of outlet channels to adjust fluid volume that passes through each respective outlet channel.

### Claim 10 (depends on 2)

The method of claim 2, wherein the source of fluid containing particles suspended therein comprises at least a first particle type and a second particle type.

### Claim 11 (depends on 10)

The method of claim 10, wherein the first particle type is red blood cells (RBCs) and the second particle type is white blood cells (WBCs).

### Claim 12 (depends on 10)

The method of claim 10, wherein the first particle type is free beads and the second particle type is beads bound to cells.

### Claim 13 (depends on 11)

The method of claim 11, wherein the migrated particles collected in a first outlet channel comprise WBCs.

### Claim 14 (depends on 1)

The method of claim 1, wherein the rate of introducing particles from the source of fluid containing particles suspended therein through the microfluidic device is in excess of 1,000 particles per second.
